The objective of our proposed research is to investigate the physiological function of histamine and its mode of action in embryonic development and implantation. The earlier theory that histamine is responsible for decidualization or implantation did not gain general acceptance and still remains obscure. Renewed interest in the role of histamine in embryo development and subsequent ovum implantation has been generated recently in this and other laboratories. Our recent findings of histamine binding with cell membranes of rabbit blastocysts and the histamine forming capacity of the latter are intriguing. Further exploration of these observations may reveal possible roles of histamine in early embryogenesis and in ovum implantation. The embryo is an "allograft". It is still conjecture how the embryo escapes immunological responses of the mother during implantation in spite of its antigenicity and the immunological competence of the mother. Histamine is proposed to act through H1 - or H2-receptors. Histamine binding to H1-receptors mediates a variety of "pro-inflammatory" effects, whereas binding with H2-receptors of lymphocytes causes suppression of a number of immune reactions. Immunofluorescent technique will be used to detect H1 or H2-receptors on blastocyst or uterine endometrial cell membranes. Lymphocyte proliferation of splenic cells under mitogen stimulation or mixing with allogenic cells in vitro in the presence or the absence of blastocyst fluid or cells with or without prior incubation with histamine will also be performed to test for their inhibitory effects. Culture and transplantation of embryos will be done to answer physiological implication of histamine in embryogenesis and implantation. Radioimmunoassay of steroids and cyclic nucleotides as well as determination of histamine content, histidine decarboxylase and histaminase activities will be performed to elucidate different aspects of embryonic and uterine tissue metabolism during embryogenesis and ovum implantation in response to histamines and antihistamines.